Can serial cerebral MRIs predict the neuronopathic phenotype of MPS II?

A.A.M. Vollebregt, B.J. Ebbink, D. Rizopoulos, M.H. Lequin, F.K. Aarsen, E.G. Shapiro, A.T. van der Ploeg, J.M.P. van den Hout*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: To advance the prediction of the neurocognitive development in MPS II patients by jointly analyzing MRI and neurocognitive data in mucopolysaccharidosis (MPS) II patients.

Methods: Cognitive ability scores (CAS) were obtained by neuropsychological testing. Cerebral MRIs were quantified using a disease-specific protocol. MRI sumscores were calculated for atrophy, white-matter abnormalities (WMA) and Virchow-Robin spaces (VRS). To distinguish between atrophy and hydrocephalus the Evans' index and the callosal angle (CA) were measured. A random effects repeated measurement model was used to correlate CAS with the three MRI sumscores.

Results: MRI (n = 47) and CAS scores (n = 78) of 19 male patients were analyzed. Ten patients were classified as neuronopathic and nine as non-neuronopathic. Neuronopathic patients had normal cognitive development until age 3 years. Mental age plateaued between ages 3 and 6, and subsequently declined with loss of skills at a maximum developmental age of 4 years. MRIs of neuronopathic patients showed abnormal atrophy sumscores before CAS dropped below the threshold for intellectual disability (

Conclusion: In our cohort, brain atrophy showed a stronger correlation to a decline in CAS when compared to WMA. Atrophy-scores were higher in young neuronopathic patients than in non-neuronopathic patients and atrophy was an important early sign for the development of the neuronopathic phenotype, especially when observed jointly with white-matter abnormalities.

Original languageEnglish
Pages (from-to)751-762
Number of pages12
JournalJournal of Inherited Metabolic Disease
Issue number3
Early online date16 Dec 2020
Publication statusPublished - May 2021


  • MPS II
  • MRI
  • hunter syndrome
  • lysosomal
  • mps ii
  • mri
  • mucopolysaccharidosis
  • neuropsychological
  • phenotype


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